Three-dimensional matrix-based models for dental tissue engineering

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The availability of in vitro 3D (dimensional) cell-based models that mimics in vivo dento-alveolar tissues is a progressively significant challenge facing oral health research and dental industry. The rising total-delivered-cost as well as the poor predictive value of the current in vitro models and assays, place great emphasis on the development of more realistic 3D cell-based models and assays. Accurate and efficient in vitro models are of enormous value, since they permit early and knowledge-based decisions in drug testing. 3D matrix-based models with different cells, in a bioreactor system that simulate dentoalveolar system, holds great potential for tissue engineering, regenerative medicine and drug discovery. The main challenge in developing 3D dentoalveolar tissue constructs is the characterization of living, biologically relevant cells in the constructs and the application of environmental factors that mimics in vivo conditions. These models will confer the advantage of speed, accuracy and scale over existing 2D monoculture-based methods. These 3D model-based technologies are critically important for understanding disease process and drug discovery. My laboratory has recently emerged at the forefront of this nascent field due to our established work on nanomaterial characterization using cell culture-based models, experiments on stem cells from apical papillae, macrophages and macrophage-stem cell interactions. We have worked on the biomechanics of dento-osseous structures, which is key to simulate environmental factors in 3D dentoalveolar models. In addition, our recent efforts to adapt the rapidly emerging 3D printing technology to print molds, generated a novel way to position immune cells and stem cells in the 3D engineered dental tissue like constructs. Building on our established work and recent success, the short term aim of this research program is to develop and characterize in vitro 3D matrix-based tissue constructs in a bioreactor platform to simulate in vivo periodontium. Complementary rapid assays will be developed for determining cell morphology, migration, proliferation, differentiation and apoptosis. Using that understanding, we will focus on developing new anatomically-based designs to integrate immune/stem cells with extracellular matrix in the constructs of dentoalveolar apparatus. These models will aid in understanding the mechanisms of interaction between immune cells and stem cells in pro- and anti-inflammatory conditions, as well as in the presence of immune modulatory nanoparticles. Over the long term we will develop integrated in vitro 3D dentoalveolar tissue construct-bioreactor platform that lower the cost, increase throughput and automate rapid assays targeted towards specific applications in drug discovery or biological research. These systems by its cost effectiveness and enhanced capabilities will improve the productivity of pharmaceutical, biological and biomedical researchers